It is known that the high blood pressure of patients with essential hypertension can be reduced using inhibitors of angiotensin converting enzyme (ACE inhibitors), such as captoprit or enalapril (Therapiewoche 29 [1979] 7746; Lancet 2 [1981] 543-546). However, a certain percentage of patients with essential hypertension do not respond to substances of this type (Drug Devel. Eval. 4 [1980] 82-91).
It has been disclosed that the antihypertensive action of enalapril or captopril is potentiated by the addition of diuretically effective amounts of a diuretic of the thiazide type of analogous compounds (Brunner et al., Clin. Exp. Hypertension 2 [1980] 639-657; McGregor et al., Br. Med. J. 284 [1982] 693-696). It is generally assumed that this effect is based on stimulation by the diuretic of the renin-angiotensin system via a loss of salt and volume (P. J. S. Chiu et al., J. Pharm. Pharmacol. 37 [1985] 105).
There is a report in Arzneim.-Forsch./Drug Res. 34 (II) [1984] 1417-1425 of investigations into the cardiovascular action of 2-[N-[(S)-1-carboxy-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2-azabicyclo[3.3. 0]octane-3-carboxylic acid ("ramiprilate"). This entailed animals being pretreated with furosemide or piretanide for several days for the purpose of sodium depletion.
We have now found, surprisingly, that ACE inhibitors combined with loop diuretics in low dosage effectively lower blood pressure.